Abstract
Osteoarthritis (OA) is the most frequent joint disease; however, the etiopathogenesis is still unclear. Chondrocytes rely primarily on glycolysis to meet cellular energy demand, but studies implicate impaired mitochondrial function in OA pathogenesis. The relationship between mitochondrial dysfunction and OA has been established. The aim of the study was to examine the differences in glucose and Fatty Acids (FA) metabolism, especially with regards to metabolic flexibility, in cybrids from healthy (N) or OA donors. Glucose and FA metabolism were studied using D-[14C(U)]glucose and [1-14C]oleic acid, respectively. There were no differences in glucose metabolism among the cybrids. Osteoarthritis cybrids had lower acid-soluble metabolites, reflecting incomplete FA β-oxidation but higher incorporation of oleic acid into triacylglycerol. Co-incubation with glucose and oleic acid showed that N but not OA cybrids increased their glucose metabolism. When treating with the mitochondrial inhibitor etomoxir, N cybrids still maintained higher glucose oxidation. Furthermore, OA cybrids had higher oxidative stress response. Combined, this indicated that N cybrids had higher metabolic flexibility than OA cybrids. Healthy donors maintained the glycolytic phenotype, whereas OA donors showed a preference towards oleic acid metabolism. Interestingly, the results indicated that cybrids from OA patients had mitochondrial impairments and reduced metabolic flexibility compared to N cybrids.
Highlights
Osteoarthritis (OA) is the most frequent joint disease, but the etiopathogenesis of OA is not entirely understood
Basal glucose and oleic acid metabolism were analyzed in cybrids by measuring acute (4 h) oxidation and uptake as well as time-course accumulation over 24 h
Mitochondrial plays critical role in maintaining functional mitochondria when cells experience a metabolic change. These results suggest that N cybrids are able to increase glucose metabolism when the Fatty Acids (FA) pathway is blocked, whereas OA cybrids were only to increase oleicwhereas acid oxidation whenwere the only glucose was blocked
Summary
Osteoarthritis (OA) is the most frequent joint disease, but the etiopathogenesis of OA is not entirely understood. It is a heterogeneous disorder where genetics as well as biomechanical, endocrine, and inflammatory effects may be involved in its origin [1]. With acceptance of the joint as an organ, the pathogenesis of OA has been viewed as a complex process that involves cartilage degradation, synovial inflammation, subchondral sclerosis, muscular atrophy, and ligament damage; all culminating in joint dysfunction [2,3]. Most cells adapt and are able to change their energy metabolism, either by increasing catabolic pathways when substrate availability is high or by increasing anabolic processes to respond to low nutrient intake [6]
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